The mechanism for the desensitization of striatal dopamine receptors appear to be heterologous. Prolonged incubation of striatal slices with D-1 receptor agonists result in a decreased responsiveness of adenylate cyclase to further stimulation by dopamine, NaF or cholera toxin. Experimental evidence indicates that the functional efficiency of the G/F protein is reduced. Prolonged incubation of striatal slices with D-1 receptor agonist is also associated with an increased phosphorylation of membrane proteins. Preincubation of striatal slices with haloperidol greatly reduces this increase, while sulpiride fails to alter the increase in phosphorylation.